Common genetic risk factors in ASD and ADHD co-occurring families

Zhou, Anbo; Cao, Xiaolong; Mahaganapathy, Vaidhyanathan; Azaro, Marco A.; Gwin, Christine; Wilson, Sherri; Buyske, Steven; Bartlett, Christopher W.; Flax, Judy; Brzustowicz, Linda M.; Xing, Jinchuan

doi:10.1007/s00439-022-02496-z

Cited by 11 publications

(16 citation statements)

References 75 publications

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“…Family and twin studies support the idea that these neurotypes share a genetic underpinning. However, the specific genetic, structural or environmental mechanisms contributing to the coexistence and overlap of these neurotypes remains to be fully elicited [ 16 , 36 ]. There is also evidence that ADHD symptoms may manifest across other diagnostic categories such as Intellectual Disability and autism, further emphasising the need to avoid rigid adherence to current diagnostic boundaries but, instead, to be led by traits and functional impairment.…”

Section: Discussionmentioning

confidence: 99%

Towards system redesign: An exploratory analysis of neurodivergent traits in a childhood population referred for autism assessment

Lang,

Wylie,

Haig

et al. 2024

PLoS ONE

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Background Children’s health services in many countries are moving from single condition diagnostic silo assessments to considering neurodevelopment in a more holistic sense. There has been increasing recognition of the importance of clinical overlap and co-occurrence of different neurotypes when assessing neurodivergent children. Using a cross-sectional service evaluation design, we investigated the overlap of neurodivergences in a cohort of children referred for autism assessment, focusing on motor, learning, and attention/activity level domains. We aimed to determine what proportion of children in a cohort referred for an autism assessment showed traits of additional neurodivergences, and what proportion were further investigated. Methods We evaluated anonymised medical records of children aged between two and 17 years referred for autism assessment. We used validated questionnaires to assess for neurodivergent traits. A weighted scoring system was developed to determine traits in each neurodevelopmental domain and a score above the median was considered to indicate a neurodivergent trait. Evidence of further investigations were recorded. We then examined the relationships between autism traits and traits of additional neurodivergence. Results 114 participants were included for evaluation. 62.3% (n = 71) had completed questionnaires for analysis. Of these, 71.8% (n = 51) scored greater than the median for at least one additional neurotype, indicating the presence of other neurodivergent traits, and 88.7% (n = 64) attracted a diagnosis of autism. Only 26.3% of children with evidence of additional neurotypes were further investigated beyond their autism assessment. Conclusions Our results demonstrate the extensive overlap between additional neurodivergent traits in a population of children referred with suspected autism and show that only a small proportion were further investigated. The use of standardised questionnaires to uncover additional neurodivergences may have utility in improving the holistic nature of neurodevelopmental assessments.

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Section: Discussionmentioning

confidence: 99%

Towards system redesign: An exploratory analysis of neurodivergent traits in a childhood population referred for autism assessment

Lang,

Wylie,

Haig

et al. 2024

PLoS ONE

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Section: Methodsmentioning

confidence: 99%

“…WGS data for the samples in the I-ASD dataset was extracted from a previous study ( Zhou et al, 2023 ). The details of sequencing and variant identification are described previously ( Zhou et al, 2023 ). The sequencing data and the variant calls are available in the National Institute of Mental Health Data Archive (NDA) under projects C1932 and C2933.…”

Section: Methodsmentioning

confidence: 99%

Dysregulation of mTOR signaling mediates common neurite and migration defects in both idiopathic and 16p11.2 deletion autism neural precursor cells

Prem,

Dev,

Peng

et al. 2024

eLife

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Autism spectrum disorder (ASD) is defined by common behavioral characteristics, raising the possibility of shared pathogenic mechanisms. Yet, vast clinical and etiological heterogeneity suggests personalized phenotypes. Surprisingly, our iPSC studies find that six individuals from two distinct ASD-subtypes, idiopathic and 16p11.2 deletion, have common reductions in neural precursor cell (NPC) neurite outgrowth and migration even though whole genome sequencing demonstrates no genetic overlap between the datasets. To identify signaling differences that may contribute to these developmental defects, an unbiased phospho-(p)-proteome screen was performed. Surprisingly despite the genetic heterogeneity, hundreds of shared p-peptides were identified between autism subtypes including the mTOR pathway. mTOR signaling alterations were confirmed in all NPCs across both ASD-subtypes, and mTOR modulation rescued ASD phenotypes and reproduced autism NPC associated phenotypes in control NPCs. Thus, our studies demonstrate that genetically distinct ASD subtypes have common defects in neurite outgrowth and migration which are driven by the shared pathogenic mechanism of mTOR signaling dysregulation.

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“…ASD has a clear genetic predisposition, and although heritability estimates for ASD range from 70% to 90%, the molecular diagnosis rate is lower than expected ( 7 ). The New Jersey Language and Autism Genetics Study (NJLAGS) investigated more than 100 families with at least one member with ASD ( 8 ). Identical twins have a higher concordance of ASD symptoms compared to dizygotic twins ( 9 ).…”

Section: Genetic and Environmental Factorsmentioning

confidence: 99%

Neuroplasticity of children in autism spectrum disorder

Chen,

Wang,

Zhang

et al. 2024

Front. Psychiatry

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder that encompasses a range of symptoms including difficulties in verbal communication, social interaction, limited interests, and repetitive behaviors. Neuroplasticity refers to the structural and functional changes that occur in the nervous system to adapt and respond to changes in the external environment. In simpler terms, it is the brain’s ability to learn and adapt to new environments. However, individuals with ASD exhibit abnormal neuroplasticity, which impacts information processing, sensory processing, and social cognition, leading to the manifestation of corresponding symptoms. This paper aims to review the current research progress on ASD neuroplasticity, focusing on genetics, environment, neural pathways, neuroinflammation, and immunity. The findings will provide a theoretical foundation and insights for intervention and treatment in pediatric fields related to ASD.

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Common genetic risk factors in ASD and ADHD co-occurring families

Cited by 11 publications

References 75 publications

Towards system redesign: An exploratory analysis of neurodivergent traits in a childhood population referred for autism assessment

Towards system redesign: An exploratory analysis of neurodivergent traits in a childhood population referred for autism assessment

Dysregulation of mTOR signaling mediates common neurite and migration defects in both idiopathic and 16p11.2 deletion autism neural precursor cells

Neuroplasticity of children in autism spectrum disorder

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